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Central Nervous System Physiology: Cerebrovascular

This chapter focuses on central nervous system (CNS) physiology and pharmacology relevant to anesthesiology. The molecular and cellular substrates of specific drugs affecting the nervous system are covered in Chapter 8 and in the appropriate chapters in this section. Cerebrovascular Anatomy The cerebral arterial vasculature is divided into anterior and posterior circulations that are interconnected through a vascular loop referred to as the circle of Willis…

Central Nervous System Physiology: Neurophysiology

The neuron is the fundamental unit of information processing and transfer in the central nervous system (CNS). It is, however, the collective activity of hierarchically organized neuronal circuits and networks that underlies its behavioral and homeostatic functions. These functions are emergent properties of a complex system. Therefore the CNS has to be examined on different organizational levels: properties characteristic of a functional unit on one level…

Adverse Drug Reactions

Definition No medicine is risk free, yet the definition of an adverse drug reaction may not be straightforward. The World Health Organization (1972 Technical Report No. 498) defines an adverse drug reaction as “A response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modifications of physiological…

Pharmacodynamic Drug Interactions

History Pharmacology is characterized by detailed descriptions of the actions of individual drugs. In the case of anesthesia, no single drug has been found to be universally satisfactory and indeed general anesthesia is now regarded as a set of desirable clinical endpoints rather than a discrete phenomenon of its own. Useful endpoints include lack of awareness and a pleasant induction and recovery; lack of movement, adequate…

Physiology and Pharmacology of Obesity, Pediatrics, and the Elderly

Anesthesiologists frequently care for patients at the extremes of age and size. These patient groups have unique features that require special consideration when formulating an anesthetic plan. The purpose of this chapter is to highlight alterations in physiology associated with these special populations, focusing in particular on how the altered physiology influences the behavior of anesthetic drugs as covered in other chapters. To translate this information…

Drug Metabolism and Pharmacogenetics

Evolutionary Perspective The biotransformation of foreign substances is based on ancient evolutionary defense mechanisms. Hundreds of millions of years ago, animals evolved to terrestrial life and began ingesting new varieties of plant life with nutrient and toxic potential. These early organisms had to detoxify and eliminate any novel toxic compounds or perish. Enzyme systems that originally existed to maintain homeostatic functions gradually adapted to process exogenous…

Pharmacokinetics of Inhaled Anesthetics

Historical Perspective The discovery of drugs with anesthetic properties was a landmark event in the history of pharmacology, medicine, and even civilization, in that it made otherwise painful surgical treatments of disease possible. Without a means of providing anesthesia, it was impossible for the modern discipline of surgery to develop. Before the discovery of anesthetic drugs, surgical intervention was limited to simple operations that could be…

Pharmacokinetic and Pharmacodynamic Principles for Intravenous Anesthetics

The science broadly referred to as clinical pharmacology is the foundation on which anesthesiologists base their therapeutic decisions, including the rational selection of anesthetics and the formulation of safe and effective dosage regimens. Focusing exclusively on intravenous anesthetics, this chapter reviews the fundamental theory and practical application of clinical pharmacology in anesthesia, including pharmacokinetics, pharmacodynamics, the “biophase” concept, compartmental models, and pharmacologic simulation. Although clinical pharmacology…

Mechanisms of Drug Action

Understanding the basic principles of pharmacology is fundamental to the practice of medicine in general, but is perhaps most relevant to the practice of anesthesiology. It is now widely accepted that cells contain a host of specific receptors that mediate the medicinal properties of drugs. Although the use of plant-derived medicinal compounds dates back to antiquity, the mechanisms by which these drugs act to modify disease…

Vagal Nerve Stimulation

Clinical Presentation The vagus nerve is the largest cranial nerve. It extends from medulla to colon, extensively supplying sensory and autonomic innervation to various thoracic and abdominal viscera. It is involved in the cardiac, pulmonary, immune, gastrointestinal, and endocrine systems. It has extensive central connection that makes it useful for neuromodulation therapies. The sensory afferent neurons end in the spinal trigeminal nucleus. The cell bodies are…

Motor Stimulation

Introduction Clinical presentation In 2013, 1.7% of the US population, or 5.4 million people, were living with paralysis. The leading causes of paralysis were stroke and spinal cord injury (SCI). Limitations brought on by any degree of paralysis significantly impact not only activity but also quality of life and emotional well-being. Patients with SCI and multiple sclerosis, another important cause of paralysis, are at 2.3 to…

Gastric Stimulation For Gastroparesis

Clinical Presentation Gastric stimulation is a treatment option typically reserved for refractory cases of gastroparesis. Estimates from Minnesota in 2007 suggest that the prevalence of confirmed gastroparesis per 100,000 people is 37.8 for women and 9.8 for men. However, estimates based on symptom profiles provide evidence that there may be a large number of undiagnosed cases, which could significantly increase the prevalence. Gastroparesis is a syndrome…

Overactive Bladder

Introduction The purpose of this chapter is to provide an overview of peripheral nerve stimulation for the treatment of overactive bladder (OAB) syndrome. OAB is common among adults worldwide, with a substantial psychological and economic burden on society. Symptoms typically include a self-reported sense of urgency to void. Other symptoms can include increased urinary frequency, nocturia, and urge incontinence. Reports of overall global prevalence have ranged…

Peripheral Neuropathy

Introduction Peripheral neuropathy is among the most common reasons patients seek out medical care. The overall prevalence in the general population is estimated to be 2.8% and increases to 8% in those older than 55 years of age. There are many causes of peripheral neuropathy, with diabetic neuropathy, vitamin deficiencies, dysproteinemias, toxin-induced (including chemotherapeutics), trauma-related, and inherited gene mutations being among those most commonly diagnosed. Peripheral…

Postamputation Pain

Introduction It is estimated that there are currently 2 million amputees living in the United States, with nearly half of these patients suffering from postamputation pain (PAP). With approximately 185,000 new amputations occurring each year, the number of amputees is expected to rise to over 3.5 million by 2020, with a corresponding increase in the incidence of PAP. Amputation permanently alters nearly every aspect of the…

Peripheral Nerve Stimulation for Chronic Pelvic Pain

Introduction Over 16 million Americans between 18 and 50 years of age are impacted by chronic pelvic pain. This pain affects sexual intercourse, relationships, sleep, the ability to sit and walk, and work productivity, and is associated with depression, anxiety, and a significant impairment in quality of life. Chronic pelvic pain is often refractory to conservative medical management. When diagnostic peripheral nerve blocks prove beneficial, peripheral…

Approach to Low Back Pain and Peripheral Nerve Stimulation

Introduction Low back pain is an extremely common presenting complaint that occurs in upwards of 80% of the population. Chronic back pain (>12 weeks’ duration) develops in a small percentage of patients. The first step in the treatment of low back pain is to evaluate for and rule out “red-flag signs.” A complete history and physical exam are critical to creating a differential diagnosis and diagnostic…

Postherpetic Neuralgia

Clinical Presentation Postherpetic neuralgia (PHN) is the most common complication of the varicella zoster virus (VZV) infection, also known as herpes varicella zoster (HVZ). PHN is a long-term, debilitating complication that occurs due to reactivation of VZV. The clinical terminology of herpes zoster is the reactivation of VZV from a dormant state. PHN is classically a burning pain that persists long after the herpes zoster rash…

Peripheral Nerve Stimulation for Complex Regional Pain Syndrome

Introduction The taxonomy complex regional pain syndrome (CRPS) was introduced in 1993 by the International Association for the Study of Pain (IASP) to describe the pain syndromes reflex sympathetic dystrophy (type 1) and causalgia (type 2). CRPS is a conglomeration of symptoms and signs involving autonomic and somatic nerve function, to a debilitating extent, with unknown pathophysiology. The IASP introduced the diagnostic criteria of disproportionate pain,…